Developing insertable cardiac monitors to assess social and environmental effects on the autonomic stress response in a nonhuman primate model of aging

开发可插入心脏监测仪，以评估社会和环境对非人类灵长类衰老模型中自主应激反应的影响

• 批准号: 10683337
• 负责人: Elizabeth Archie
• 金额: $ 28.88万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10683337
• 关键词: Acceleration; Accelerometer; Acute; Adult; Affect; Aging; Animal Model; Animals; Autonomic nervous system; Biological Assay; Calibration; Cardiac; Cardiometabolic Disease; Chronic; Chronic stress; Data; Diabetes Mellitus; Dimensions; Electrocardiogram; Energy Metabolism; Event; Face; Famines; Glucocorticoids; Goals; Grain; Health; Heart Diseases; Heart Rate; Hour; Human; Implant; Individual; Kenya; Lead; Life; Life Cycle Stages; Life Experience; Link; Longevity; Longitudinal Studies; Measures; Mediating; Metabolic; Metabolism; Mission; Modeling; Monitor; Neurosecretory Systems; Papio; Physical activity; Physiology; Population; Poverty; Primates; Process; Prognostic Marker; Proxy; Public Health; Recovery; Research; Rest; Risk Behaviors; Shapes; Social Conditions; Social Environment; Social isolation; Stress; Testing; Time; Validation; Walking; Work; acute stress; biological adaptation to stress; cardiometabolism; cardiovascular disorder risk; cost; disorder risk; doubly-labeled water; early life adversity; environmental stressor; experience; heart rate variability; hypothalamic-pituitary-adrenal axis; mortality; neglect; nonhuman primate; obesity risk; prospective; psychosocial; response; social; social adversity; social stressor; stressor; tool

Project Summary The long reach of early life remains one of the most enduring puzzles in human health. From famine to poverty and neglect, adverse early life experiences lead to higher mortality and elevated risk for obesity, diabetes, and chronic heart disease. These effects are likely mediated, in part, by the stress response, a cascade of neuroendocrine, metabolic, and cardiac responses to challenge involving the hypothalamic– pituitary–adrenal (HPA) axis and the autonomic nervous system. In support, several leading hypotheses propose that repeated social and environmental stressors—both in early life and adulthood—cause over- activation of the stress response, chronic stress, and accelerated aging. Long-term studies of natural animal populations offer compelling models for testing these ideas because they often have fine-grained, prospective, longitudinal data on social and environmental stressors from individuals across the life course. However, natural animal models also face considerable challenges in measuring multiple facets of the stress response: most are constrained to measuring glucocorticoids (GCs) as the sole measure of stress responses, reflecting just one aspect of the HPA axis with no information on autonomic responses. This limitation has led many to call for expanded tools to measure stress responses in natural animal models of aging. Our objectives in this proposal are to: (1) expand the tools for measuring the cardiometabolic consequences of stress in natural animal models by validating insertable cardiac monitors (ICMs) with accelerometry to measure heart rate, heart rate variability, and physical activity; and (2) test the social and environmental drivers of the autonomic stress response and its metabolic consequences. We will develop and validate ICMs using captive baboons at the Institute of Primate Research in Kenya, and a well-studied, natural population of baboons in Amboseli, also in Kenya. Prior work in Amboseli has already shown that an accumulation of harsh conditions in early life and social isolation in adulthood exert profound effects on adult mortality, setting the stage to probe the stress responses underlying these links. While early life adversity and social isolation lead to elevated GCs in adulthood, and animals with high lifelong GCs have lower survival, GCs do not mediate the link between early adversity and life span. Gaining a broader perspective on individual stress responses and their consequences is an essential next step. The results will contribute the first prospective, longitudinal data in any species to understand how early life adversity and adult social conditions interact to shape acute autonomic stress responses, chronic stress, and energy expenditure. This study will provide a direct link between socio-environmental circumstances, stress responses, and adult health, helping to identify key targets to mitigate the effects of stress over the life course on aging.

项目概要 从饥荒到生命早期，生命的长期影响仍然是人类健康中最持久的难题之一。 贫困和忽视、不良的早期生活经历导致更高的死亡率和肥胖风险， 这些影响可能部分是由压力反应介导的。 涉及下丘脑的神经内分泌、代谢和心脏对挑战的级联反应 垂体-肾上腺（HPA）轴和自主神经系统支持几个主要假设。 提出重复的社会和环境压力——无论是在早年还是成年——会导致过度 应激反应的激活、慢性应激和加速衰老的天然动物的长期研究。 人们提供了令人信服的模型来检验这些想法，因为他们通常有细粒度的、前瞻性的、 然而，个人整个生命过程中社会和环境压力的纵向数据。 自然动物模型在测量应激反应的多个方面也面临着相当大的挑战： 大多数人仅限于测量糖皮质激素（GC）作为应激反应的唯一测量方法，反映了 只是 HPA 轴的一个方面，没有有关自主反应的信息。这一限制导致许多人 呼吁扩大工具来测量自然衰老动物模型中的应激反应。 我们在该提案中的目标是：（1）扩展测量心脏代谢的工具 通过验证插入式心脏监测仪 (ICM) 来了解自然动物模型中的压力后果 加速度测量法测量心率、心率变异性和体力活动；(2) 测试社交和身体活动； 我们将开发和研究自主应激反应及其代谢后果的环境驱动因素。 在肯尼亚灵长类研究所使用圈养狒狒和经过充分研究的天然狒狒验证 ICM 同样在肯尼亚的安博塞利的狒狒种群先前的研究已经表明， 早年恶劣条件的积累和成年后的社会孤立对成年产生了深远的影响 死亡率，为探讨这些联系背后的压力反应奠定了基础。 社会隔离导致成年期 GC 升高，终生 GC 较高的动物存活率较低，GC 不调解早期逆境和寿命之间的联系 获得更广泛的个人视角。 压力反应及其后果是下一步至关重要的结果将有助于第一步。 任何物种的前瞻性纵向数据，以了解早期生活逆境和成年社会条件如何 这项研究将相互作用来塑造急性自主应激反应、慢性应激和能量消耗。 提供社会环境条件、压力反应和成人健康之间的直接联系，帮助 确定减轻生命过程中压力对衰老影响的关键目标。